Abstract: BACKGROUND: Hyperoside has many pharmacological effects such as anti-inflammation and anti-oxidation, but there are few studies on its application in repairing endometrial injury. 
OBJECTIVE: To prepare hyperoside nanoparticles and to study the repairing effect of poloxamer 407 carrying hyperoside nanoparticles on endometrial injury in model rats. 
METHODS: Hyperoside nanoparticles, poloxamer 407 hydrogel and poloxamer 407 hydrogel with hyperoside nanoparticles were prepared separately. Twenty-four female SD rats were randomly divided into four groups (n=6): model group, blank control group, hydrogel group, and drug-loaded hydrogel group. Rat models of endometrial injury were established by scratching method in the model group, hydrogel group and drug-loaded hydrogel group. PBS, poloxamer 407 hydrogel and poloxamer 407 hydrogel with hyperoside nanoparticles were injected into the uterus of rats in the model group, hydrogel group and drug-loaded hydrogel group. The blank control group received only laparotomy without modeling. The model was taken 7 days after the injection. The morphological changes of rat endometrium were observed by hematoxylin-eosin staining. The expression of interleukin-1β, interleukin-8, and tumor necrosis factor-α in the endometrial tissue of rats in each group was detected by ELISA. Immunofluorescence staining was used to detect the expression of vascular endothelial growth factor, keratin and vimentin in endometrial tissue.
RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining showed that compared with the blank control group, the endometrial layer of the rats in the model group became thinner, the endometrial structure was incomplete, and the blood vessels and glands were significantly reduced and sparse. Compared with the model group, the endometrium of the rats in the hydrogel group was thickened and the endometrial structure was relatively complete. The endometrial structure of the rats in the drug-loaded hydrogel group was thickened, the endometrial structure was relatively complete, and the glands were more abundant. (2) Compared with the blank control group, the levels of interleukin-1β, interleukin-8, and tumor necrosis factor-α were all increased in the model group (P < 0.01). Compared with the model group, the levels of interleukin-1β, interleukin-8, tumor necrosis factor-α decreased in the hydrogel group and drug-loaded hydrogel group (P < 0.01). (3) Immunofluorescence staining showed that compared with the blank control group, the expression levels of vascular endothelial growth factor, keratin and vimentin were decreased in the model group (P < 0.01). Compared with the model group, the expression levels of vascular endothelial growth factor, keratin and vimentin were all increased in the drug-loaded hydrogel group (P < 0.01), and the expression of vascular endothelial growth factor was increased in the poloxamer 407 group (P < 0.01). (4) These results confirm that hydrogel carrying hyperoside nanoparticles has a repairing effect on the rat endometrial injury model. 

Key words: hyperoside, hydrogel, poloxamer 407, endometrial injury, ion crosslinking method, nanoparticle, tissue repair